Type II Diabetes Mellitus: An Emerging Epidemic Andy ChristensenNSCI 411 March 1, 2005 Diabetes is a group of metabolic disorders characterized by inadequate insulin secretion by the pancreas or cellular destruction leading to an insulin deficiency. Depending on the cause of the insulin shortage, diabetes can be sub categorized into type I and type II. Type I diabetes (T 1 DM) is usually mediated by the destruction of b-cells in the pancreas resulting in decreased insulin production and secretion. Type II diabetes (T 2 DM) is the failure of these b-cells to secrete adequate amounts of insulin to compensate for insulin resistance and increased gluconeogenesis combined with an overall resistance to the insulin action (8., 1997).

T 2 DM accounts for 90 to 95 percent of all diabetes cases. While T 2 DM is traditionally viewed as an adult disease, its prevalence among children and adolescents is becoming a major medical crisis, particularly targeting minorities and those genetically prone, and resulting from the rising obesity rates, sedentary lifestyles, and dietary indiscretions. The disease is more commonly found in minorities, predominantly African Americans, Mexican Americans, and Native Americans. Studies of African American children have shown that compared to Caucasian children they have higher rates of, increased b-cell activity, reduced insulin clearance, lower insulin sensitivity, and higher obesity risks (Arslanian, 2002). Although it is unclear if these factors are due to racial intrinsic differences, lifestyle, genetics, or other biological factors, these issues could easily explain the higher prevalence of T 2 DM among minorities.

It is most accepted that a combination of these factors is the primary cause for the relationship between race and diabetes. Some of the symptoms associated with type II diabetes include, polyphagia, and polydipsia. At diagnosis, 33 percent of patients have ketonuria, and 5 to 25 percent have, both of which can be tested for by simple urinalysis (American Diabetes Assoc. 2000). Most patients of T 2 DM are obese with little to no weight loss, which allows doctors to distinguish them from type I diabetics. The total lack of insulin among type I diabetics, or insulin dependent diabetics, will result in problems in the storage of fat and muscle proteins causing the body to break them down.

Hence, type I diabetics can be distinguished often by weight loss. Other symptoms such as damage to the kidneys, eyes, nerves, heart, and blood vessels can occur if the diabetes goes unnoticed for a prolonged period of time and glucose levels are not controlled (Novitt-Moreno, 1996). The detection of T 2 DM can be difficult because the patient may or may not have many of the symptoms depending on how severe their case is. Many of the symptoms are very similar to those of type I diabetes making classification difficult. Some patients are found to have glucosuria upon routine urinalysis, which could lead to the diagnosis. Ketonuria can also be detected but usually only occurs in only one forth of patients who have type II diabetes.

Simple clinical features of T 2 DM can assist doctors diagnosing and classifying the disease. More than 85 percent of patients diagnosed are overweight or obese. A family history of type II diabetes is found in the majority of patients who are known to have T 2 DM. A skin condition known as nig ricans is also common and can be detected by routine physical examination. It is characterized by hyper pigmentation and a velvety texture caused by long-standing and usually is found around the neck, inner thighs, and ante cubital areas (Nesmith 2001).

In addition to clinical signs, laboratory tests and evaluations are necessary to classify a person accurately. Diagnostic tests include fasting plasma glucose, random plasma glucose, hemoglobin (HbA 1 c) measurements, and oral glucose tolerance testing. All tests are aimed at measuring the blood glucose levels of a patient and comparing them statistically with normal glucose levels of a population. One major problem for these tests is that they may not be accurate in predicting the onset of diabetes. The tests are used to determine what glyceric level would be appropriate to begin treatment for the body's insulin resistance (Sadovsky, 2003).

Since a normal person's glucose level rises and falls within a certain value each day, getting an accurate value from a patient can often be difficult and could depend on many factors such as time of day and time of last meal. Most doctors recommend that adults, particularly overweight adults, be screened at least every two years. Although diabetes cannot be cured most type II diabetics are not insulin dependent and their symptoms can usually be treated or prevented by regular exercise and a healthy diet. In some cases serious ailments can occur due to insulin resistance, excess hepatic glucose production, and lower insulin secretion by the pancreas.

For treating type II diabetes, there are two major types of drugs that are commonly used: those that increase the body's insulin supply and those that decrease the resistance of insulin or increase its effectiveness (, ). Other types of drugs that are less popular include alpha- inhibitors, which reduce the rate of glucose absorption, and weight loss agents (Abramowitz, 2002). Sulfonylureas stimulate the production and release of insulin by binding to the b-cells of the pancreas. The site of action is the trans membrane region that makes up the ATP-sensitive potassium channels. The depolarization of the membrane causes an influx of calcium stimulating insulin secretion into the blood stream. The effectiveness of these drugs is very high (90-95%) but the use of can lead to hypoglycemia, especially in the elderly and those with impaired renal or hepatic function.

Some of the drugs on the market today include, , , and. Other non-, such as and, are structurally different but have similar modes of action in that they bind to the ATP-sensitive potassium channels on b-cells. These drugs are usually as effective and do not cause hypoglycemia in as many cases as the, therefore making them safe for patients with renal impairments. These are usually taken right before a meal causing plasma levels of insulin to peak within 30-60 minutes and return to baseline before the next meal (Abramowitz, 2002). Metformin, the only approved marketed in the US, mainly decreases hepatic glucose production and increases peripheral glucose utilization. It is about as effective as (about 90-95% effective) and can be taken once daily.

Metformin does not cause hypoglycemia and can result in a small weight loss of about 2 to 3 kg due to the gastrointestinal effects associated with its use including nausea, diarrhea, and abdominal pain. The level of pain seems to be related to the size of the dosage, so discomfort can usually be controlled by reducing the dosage. Some fatal incidents of lactic acidosis (about 9 cases/100,000 patients-year), especially in patients with renal diseases, have been caused by use of (Rendell and Kirchain, 2000). These incidents are very low and can be easily prevented. Thiazolidinediones decrease insulin resistance and increase insulin sensitivity in adipose tissue similarly to. Although the mode of action is not clear for, it is certain that the drug enhances glyceric control when used along with treatment (Abramowitz, 2002).

Type II diabetes is a progressive disorder in which hyperglycemia usually increases over time. After about 3 years of treatment, 50% of patients need a second drug to control their blood glucose levels. After 9 years, the proportion increases to 75%. Because oral agents generally achieve 70-80% of their maximum effectiveness with half of the recommended maximum dose, adding a second drug is preferred over increasing the dosage of a single drug. The most common combination therapy for T 2 DM is a taken with. As the disease progresses a third drug is generally added.

Usually, the third treatment would be directly administered insulin (Abramowitz, 2002). Since over 80% of patients with type II diabetes are over weight, weight loss is becoming as important to its treatment as insulin is to type I diabetes. The epidemic of T 2 DM in our society is a result of sedentary life styles and poor eating habits; both of which are hard to maintain in patients with weight problems. Several agents have been produced to help facilitate weight loss but all have encountered major obstacles in clinical use. The most effective way to treat and prevent diabetes II is to maintain a healthy weight by regular exercise and a sensible diet.

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